Pattern formation is the activity by which embryonic cells form ordered spatial arrangements of differentiated tissues. The physical complexity of higher organisms arises during embryogenesis through the interplay of cell-intrinsic lineage and cell-extrinsic signaling. Inductive interactions are essential to embryonic patterning in vertebrate development, from the earliest establishment of the body plan, to the patterning of the organ systems, to the generation of diverse cell types during tissue differentiation (Davidson, Development 108:365-389 (1990); Gurdon, Cell 68:185-199 (1992); Jessell et al., Cell 68:257-270 (1992)).
The effects of developmental cell interactions are varied. Typically, responding cells are diverted from one route of cell differentiation to another by inducing cells which differ from both the uninduced and induced states of the responding cells. Sometimes cells induce their neighbors to differentiate like themselves (homogenetic induction); in other cases a cell inhibits its neighbors from differentiating like itself. Cell interaction in early development may be sequential, such that an initial induction between two cell types leads to a progressive amplification of diversity. Moreover, inductive interactions occur not only in embryos, but also in adult cells, and can act to establish and maintain morphogenetic patterns as well as induce differentiation (Gurdon (1992)). These interactions are thought to explain how distinct cell types emerge from a group of cells that have otherwise equivalent potentials.
Genetic and biochemical studies in invertebrates have shown that one means by which a signal may be transmitted is via the Notch/Lin-12/Glp-1 family of transmembrane proteins (Artavnis-Tsakonas et al., Science 268:225-232 (1995)). These proteins are thought to serve as receptors which are activated upon binding a member of the emerging DSL (Delta-Serrate-Lag-2) family of putative ligands (Tax et al., Nature 368:150-154 (1994)). Members of the DSL family are also transmembrane proteins, and activation of the receptor appears to require contact with an adjacent cell.
Three highly conserved vertebrate Notch receptor family members have also been identified, each of which is widely expressed during embryogenesis (Artavnis-Tsakonas et al., 1995). Additionally, vertebrate members of the DSL family have recently been identified (Henrique et al., Cell 80:909-918 (1995); Henrique et al., Nature 375:787-790 (1995); Chitnis et al., Nature 375:761-766 (1995); and Bettenhausen et al., Development (1995, in press)), fueling the speculation that the process of lateral cell signaling occurs in vertebrates in a manner similar to invertebrates. However, the molecular signals which regulate the cell interactions, signalling and pattern formation in this pathway and others are currently not well understood.